Bugs and Drugs Handbook PDF Free Download

Bugs and Drugs Handbook 2017 Allegra CdeBaca Age 8

Table of Contents How to Improve Infectious Disease Outcomes and Reduce Costs Sutton s Law: Culture Where the Infection Is!... 1 Legend for Antimicrobial Tables... 2 Antibiogram Table 1 - Staphylococci... 3 Antibiogram Table 2A and 2B - Streptococci... 4-5 Antibiogram Table 3 Gram Negative Organisms Non-Urine... 6 Antibiogram Table 4 Gram Negative Organisms Urine... 7 Antibiogram Table 5 Gram Negative Orgs Non-Enterobacteriaceae... 8 Antibiogram Table 6 Candida spp... 9 Antibiogram Table 7 Anaerobes... 10 Microbiology Testing Schedule... 11 Multiplex PCR Information...12-13 Culture Collection and Testing Information...14-17 Critical and Urgent Value Reporting Policy for Microbiology... 18 Blood Isolates... 19 MRSA and VRE Rates...20-21 Influenza Virus Treatment...22-24 Guidelines for Changing from IV to PO Antibiotics in Hospitalized Children...24-25 Antimicrobial Formulary at Children s Hospital Colorado...27-37 Collection Guidelines for Antimicrobial Levels...38-40 Page

Bugs and Drugs Authorship For additional copies of this book, please come to the Microbiology Laboratory in the lower level of the East Tower or print a copy from https://info.childrenscolorado.org/dept2/home/lab/documents/2016_drugsandbugs_handbook.pdf. Children s Hospital Colorado Microbiology Laboratory 13123 E. 16 th Ave., Box B120 Aurora, CO 80045 720-777-6703 Thanks to the following contributors to this booklet: Sam Dominguez, MD, PhD Medical Director, Clinical Microbiology Laboratory Associate Medical Director, Infection Prevention and Control James K. Todd, MD Consulting Medical Director, Clinical Microbiology Laboratory Medical Director, Epidemiology Sarah Parker, MD Medical Director, Antimicrobial Stewardship Stacey Hamilton, MT, SM (ASCP) Microbiology Manager Elaine Dowell, MT, SM (ASCP) Senior Manager Microbiology and Molecular Operations Christine Robinson, PhD Scientific Director Virology and Molecular Microbiology Andrea Prinzi, MLS, SM (ASCP) Antimicrobial Specialist Abigail Pride, MLS (ASCP) Antimicrobial Specialist Jason Child, PharmD Infectious Disease Pharmacist Amanda Hurst, PharmD Infectious Disease Pharmacist Ann-Christine Nyquist, MD, MSPH Medical Director, Infection Prevention and Control Robert Snyder, MT (ASCP) Chemistry Manager Carolyn Brock Senior Administrative Professional, Epidemiology Kelly Pearce Data Analyst, Epidemiology Bradley T. Anderson, MD Resident Physician, Medical Education Robin Ortenberg, MD Resident Physician, Medical Education Children's Hospital Colorado

How to Improve Infectious Disease Outcomes and Reduce Costs Sutton s Law: Culture Where the Infection Is! Key Principles for Culturing and Antimicrobial Use: 1. Garbage In, Garbage Out Don t get cultures if you won t know how to interpret the result. This often applies to surface (skin, mucous membranes) cultures that are always colonized with normal flora. 2. Tissue is the Issue Don t use swabs; get a tissue biopsy or needle aspirate. Bacteria are absorbed into and die on swabs. 3. Sutton s Law: Culture where the infection is Blood cultures will only be positive <=50% of the time in children who have serious bacterial infections. Get a relevant non-permissive focus culture as well as blood cultures before starting antibiotics. 4. One is not enough Before starting antibiotics (especially in very sick or immunocompromised children) get at least two blood cultures with separate preps (even through the same central line). That way you can interpret a positive culture growing a relative non-pathogen. 1

2016 Annual Antibiogram Tables 1 8 Legend for Antibiogram Tables Indicates first-line therapy, with susceptibility between 75-100%. This medication has good penetration, limited side-effects and overall strong susceptibilities. Second-line. Susceptibility between 75-100%, but not first choice due to overly broad-spectrum, toxicities, or both. May be appropriate as initial therapy before specific bacteria has been identified. Susceptibility between 50-74%. Not initial treatment of choice, but can be used if other medications are not available, patient has significant allergies, or susceptibility known. Susceptibility for these medications is less than 50%. Consult ID prior to using these medications and/or use only if known susceptible. - Not tested. - R This organism is known to have intrinsic resistance to this antibiotic. S This organism is known to be susceptible to this antibiotic. 2

NUMBER OF ISOLATES TESTED Vancomycin Clindamycin Trimethoprim / Sulfa Oxacillin* TABLE 1. Gram Positive Organisms: Staphylococcus (% Susceptible) Antimicrobial Susceptibilities at Children s Hospital Colorado 2016 ANTIMICROBIALS ORGANISMS Staph aureus (MSSA) 808 100 82 100 100 Staph aureus (MRSA) 437 100 76 98 R Staph epidermidis 190 100 45 66 35 Staph hominis 43 100 45 86 40 * Includes agents: Nafcillin/Dicloxacillin/Methicillin. If susceptible, also susceptible to cefazolin/cephalexin. Oxacillin resistance (MRSA) predicts resistance to ALL beta-lactams including penicillin, extended spectrum penicillins and cephalosporins. Confirmation of MRSA is done by PBP2, Cefoxitin Screen or Microscan Panel Cefoxitin is tested as a surrogate for oxacillin. Oxacillin susceptible or resistant is based on the Cefoxitin Screen result. Clindamycin susceptibility is not determined by Cefoxitin Screen or oxacillin resistance. The Inducible Clindamycin Test detects inducible clindamycin resistance, due to the erm genes. The isolate is presumed resistant to clindamycin when the Inducible Clindamycin Test is positive. Testing by Microscan Microtiter Panel. 3

NUMBER OF ISOLATES Penicillin Ampicillin/Amoxicillin Vancomycin Clindamycin Ceftriaxone TABLE 2A. Gram Positive Organisms - Streptococcus and Enterococcus (% Susceptible) Antimicrobial Susceptibilities at Children s Hospital Colorado 2016 ANTIMICROBIALS ORGANISMS Viridans Strep Group 1 Invasive* 48 50-100 96 81 Strep. anginosus Group 1 Invasive (23) 100-100 100 100 Beta Strep Group A 1 Invasive (26) 100 S S 96 S Beta Strep Group B 1 (7) 100 S S 75 S Beta Strep Group B 1 (prenatal screens) 498 100 S 100 58 S Enterococcus faecalis 2 143-99 100 - - Enterococcus faecium 2 52-65 100 - - Vanc Resistant Enterococcus spp. (VRE)** (9) R R R - - 1 Testing is by Microscan microtiter panel. ( ) = small number 2 Testing is by Microscan microtiter panel. Streptococci: The Inducible Clindamycin Test (D-test) detects inducible clindamycin resistance due to the erm gene. For streptococci, resistance to clindamycin is presumed when the D-Test is positive. * Most non-susceptible viridans group streptococci are intermediate to penicillin, not resistant, and may be treatable with high dose ampicillin/amoxicillin. Streptococci susceptible to penicillin are assumed susceptible to ampicillin. Enterococci: **Four new VRE patients were identified in 2016. For therapy choices, ID consult recommended Some species of enterococci are inherently resistant to vancomycin but usually not resistant to ampicillin, these are E. gallinarum and E. casseliflavis; they are not considered VRE. Combination therapy should be used in serious Enterococcus spp. Infection (endocarditis and bacteremia). Gentamicin Synergy Screen E. faecalis = 88% susceptible Gentamicin Synergy Screen E. faecium = 94% susceptible Gentamicin Synergy Screens on VRE isolates show 89% are susceptible at CHCO. 4

IV Penicillin IV Ceftriaxone Erythromycin Clindamycin Trimethoprim/Sulfa Vancomycin TABLE 2B. Gram Positive Organisms: Streptococcus pneumoniae (% Susceptible) Antimicrobial Susceptibilities at Children s Hospital Colorado - 2016 Source Number CSF (1) Blood or Sterile Aspirate Insufficient numbers of isolates to report antibiogram. Patients with pneumococcal meningitis should be started on vancomycin and ceftriaxone until susceptibilities are available. 32 81* 93 65 88 71 100 Respiratory 69 59* 94 66 91 74 100 ( ) = small numbers * Refer to organism specific susceptibility. Isolates in the intermediate category to penicillin may be treated with high dose ampicillin/amoxicillin unless in the CNS. S. pneumoniae isolates that are susceptible to penicillin are also susceptible to ampicillin (and amoxicillin if oral choice is appropriate). Ceftriaxone susceptibility does not imply susceptibility to oral cephalosporins. Erythromycin susceptibility implies susceptibility to azithromycin. 5

NUMBER OF ISOLATES Ampicillin / Amoxicillin Cefazolin Ceftriaxone Gentamicin Trimethoprim / sulfa Ciprofloxacin Meropenem Cefepime TABLE 3. Gram Negative Organisms, Non-Urine (% Susceptible) Antimicrobial Susceptibilities at Children s Hospital Colorado 2016 ANTIMICROBIALS ORGANISMS Haemophilus influenzae* Beta-lactamase testing all isolates 75 No further testing is routinely performed for betalactamase negative isolates. These isolates are considered ampicillin susceptible. Haemophilus influenzae* Beta-lactamase pos and sterile sites 45 19-100 - 49 - - - Escherichia coli 137 51 85 91 92 71 81 99 94 Enterobacter cloacae complex 61 R R IB** 95 90 98 100 95 Klebsiella pneumoniae 63 R 94 98 98 87 98 98 98 Klebsiella oxytoca 50 R 76 96 94 92 100 100 98 Serratia marcescens 33 R R IB** 97 97 100 97 100 osalmonella species 30 83 97 97-100 100 100 97 Shigella species (2014-16) (23) 61-100 - - 100 100 100 ( ) = small numbers Haemophilus was tested by E-test, all others by Microscan microtiter panel. *75 Haemophilus influenzae isolates were tested for beta-lactamase production; 47 (62%) were negative and therefore considered to be ampicillin susceptible. Haemophilus influenzae isolates that tested positive for beta-lactamase production are still considered susceptible to ampicillin-sulbactam or amoxicillin-clavulanic acid **When IB is indicated above, the organism may have an inducible beta-lactamase. Although the MIC may indicate susceptibility, beta-lactams should only be used in combination with a drug from another class to which the organism is susceptible. Cefepime and meropenem are exceptions and may be used alone. 6

NUMBER OF ISOLATES Ampicillin / Amoxicillin Ampicillin/Sulbactam Cephalothin* Cefuroxime Cefotaxime/ Ceftriaxone Gentamicin Nitrofurantoin Trimethoprim / sulfa Ciprofloxacin Ceftazidime Levofloxacin Cefepime TABLE 4. Gram Negative Organisms Isolated from Urine (% Susceptible) Antimicrobial Susceptibilities at Children s Hospital Colorado 2016 ANTIMICROBIALS ORGANISMS C. freundii complex (24) R R R R IB** 92 83 67 92 83 100 100 E. coli 1556 53 60 75 95 96 94 98 72 92 97 92 97 Enterobacter cloacae complex 36 R R R R IB** 97 50 89 97 78 97 100 Klebsiella pneumoniae 126 R 79 88 92 96 96 71 90 97 98 98 98 Klebsiella oxytoca 41 R 78 78 95 100 100 98 88 100 100 100 100 Proteus mirabilis 56 82 86 93 100 100 88 R 84 93 100 93 100 Pseudomonas aeruginosa ( ) Small number of isolates 57 R R R R R 95 R R 95 95 95 95 Testing by Microscan microtiter panel * Cephalothin results are a surrogate to predict susceptibility to the oral cephalosporin agents: cephalexin, cefuroxime, cefpodoxime, and cefdinir. Notably for lower tract infection, low level resistance can often be overcome by high-end dosages due to high concentrations of these agents in the urine. **When IB is indicated above, the organism may have an inducible beta-lactamase. Although the MIC may indicate susceptibility, beta-lactams should only be used in combination with a drug from another class to which the organism is susceptible. Cefepime and meropenem are exceptions and may be used alone. 7

NUMBER OF ISOLATES Ceftazidime Aztreonam Levofloxacin Tobramycin Meropenem Minocycline Trimethoprim / Sulfa Ciprofloxacin Gentamicin Cefepime TABLE 5. Non-Enterobacteriaceae (% Susceptible) Antimicrobial Susceptibilities at Children s Hospital Colorado 2016 ANTIMICROBIALS ORGANISMS Pseudomonas aeruginosa Non CF 1 163 93 81 84 95 94 - - 85 82 92 CF-mucoid 2 (22) 64 73-54 73 - - 54 - - CF-nonmucoid 2 (27) 78 63-55 63 - - 52 - - Stenotrophomonas maltophilia 2 59 22-66 - R 97 95 - - - 1 Non-CF testing performed by Microscan microtiter plate. 2 Cystic fibrosis (CF) Pseudomonas spp. isolates and S. maltophilia isolates tested by E-test. ( ) small number of isolates. 8

Antifungal TABLE 6. Candida species (# of Isolates Susceptible) Antimicrobial Susceptibilities at Children s Hospital Colorado 2016 C. albicans C. parapsilosis C. glabrata 7 tested 13 tested 2 tested Interpretation S SDD R S SDD S SDD R 5-Flucytosine 6-1 13-2 - - Anidulafungin 7 - - 13-2 - - Fluconazole 7 - - 12 1-2 - Micafungin 7 - - 13-1 - 1 Voriconazole 7 - - 13 - - - - Itraconazole 7 - - 13 - - - - Testing performed by UCH Amphotericin and posaconazole - there are no interpretable standards for susceptibility. ID consultation required to request. SDD - Susceptible Dose Dependent The susceptible dose dependent category implies that susceptibility of an isolate is dependent upon the dosing regimen that is used in the patient. It is necessary to use a dosing regimen (higher doses, more frequent doses or both) that results in high drug exposure. ID consult recommended. *C. krusei is intrinsically resistant to fluconazole (isolates not tested). Sources from where yeast was isolated: Blood - 8 Respiratory - 7 Stool 2 Shunt 2 Wound - 1 Urine 1 Aspirate - 1 9

Number of Isolates Ampicillin-sulbactam (Unasyn) Number of Isolates Piperacillin/tazobactam (Zosyn) Number of Isolates Cefoxitin B. fragilis group 2580 82 6 3959 87 7 3841 65 7 3939 98 1 3839 48 42 3981 98 1 Number of Isolates Meropenem Number of Isolates Penicillin/ampicillin* Number of Isolates Clindamycin Number of Isolates Metronidazole 10 Table 7. Cumulative Antimicrobial Susceptibility Report for Anaerobic Organisms Isolates Collected from Selected US hospitals Jan 2010 through December 2012 ANTIMICROBIALS ANAEROBIC ORGANISMS Percent Susceptible (%S) and Percent Resistant (%R) Fusobacterium nucleatumnecrophorum % S % R % S % R % S % R 27 100 0 27 100 0 27 100 0 27 100 0 44 100 0 27 100 0 27 100 0 % S % R % S % R % S % R % S % R Anaerobic gram- positive cocci 150 88 9 614 99 0 148 94 3 614 98 1 168 100 0 614 79 16 611 96 3 P. acnes 58 100 0 58 100 0 58 100 0 58 100 0 34 100 0 91 9 Data adapted from CLSI M100-S26 January 2016. Isolates collected from selected US hospitals.

Microbiology Testing Schedule Microbiology CSF Gram Stain 45 minutes Blood Culture 5 days to final negative BCID on positive blood culture 3 hours Strep Only Culture 1 day to prelim, 48 hours to final Tissue or Aspirate Bacterial Culture 5-7 days to final negative Urine Culture, Clean Catch 24 hours to final report Urine Culture, Catheter 48 hours to final negative Fungus Culture 4 weeks to final negative Mycobacterial Culture 6 weeks to final negative Quantiferon IGRA for TB Tues, Thurs and Fri Gastrointestinal Pathogen PCR 3 hours Respiratory Pathogen PCR (Inpatient) 3 hours Meningitis/Encephalitis Pathogen PCR 3 hours C. trachomatis/n. gonorrheae (GC) PCR 5 hours MRSA PCR 3 hours Pertussis PCR Daily Monday-Friday Influenza PCR HSV PCR HSV Culture CMV PCR CMV Culture EBV PCR EBV Serology Adenovirus PCR HHV-6 PCR Enterovirus PCR Virology 3 hours (only order during flu season) Daily Rapid culture 1 day, standard culture 7 days Daily Monday -Friday Rapid culture 2 days, standard culture 21 days Daily Monday - Friday Mondays and Wednesdays (IgM only on Friday) Monday, Wednesday and Thursday Monday, Wednesday and Thursday CSF 3 hours All other sources performed once daily 11

Multiplex PCR Panel Information MEP (Meningitis/Encephalitis Pathogen Panel) The Meningitis/Encephalitis Pathogen Panel tests for 14 pathogens associated with meningitis/encephalitis. Testing is orderable in Epic for CSF by one of two avenues: -Automatic MEP: CSF will be tested regardless of CSF cell count. Order is recommended if the patient meets one of these criteria: patient is less than 2 months of age, patient has been diagnosed with encephalitis, patient is immunocompromised, or test is approved by Infectious Disease or Neurology. -Conditional MEP: CSF will only be tested if the CSF white cell count is greater or equal to 5. Order is recommended for all patients not meeting the above requirements for automatic MEP. Bacteria Viruses Yeast Escherichia coli Cytomegalovirus Cryptococcus neoformans Haemophilus influenzae Enterovirus Listeria monocytogenes Herpes simplex virus 1, 2* Neisseria meningitidis HHV6 DNA detected Streptococcus agalactiae Parechovirus Streptococcus pneumonia Varicella-zoster virus Positive results for any bacteria, Cryptococcus, HSV 1/2 or VZV are reported directly to the provider. Positive results for CMV, enterovirus, HHV-6 or parechovirus are reported to Antimicrobial Stewardship from 8am-5pm Monday-Friday and they relay the report to the clinician. On weekends, holidays and outside of regular hours, the report is phoned directly to the clinician. Samples from Network of Care (NOC) are sent to Children s Anschutz Campus for processing. *HSV PCR may be initially negative when sampling is performed early in disease course. Consider a repeat tap and HSV PCR if clinically indicated. GIP (Gastrointestinal Pathogen Panel) The GIP (Gastrointestinal Pathogen Panel) tests for 17 pathogens associated with infectious gastroenteritis. Positive GIP results for C. difficile are not reported on stools from children under a year of age. Consider ordering Clostridium difficile PCR instead of GIP if C.difficile is the only clinical concern in patients of any age. Stool samples must be liquid to perform testing. Samples from Network of Care (NOC) are sent to Children s Anschutz Campus for processing. Bacteria Parasites Viruses Campylobacter species Cryptosporidium species Adenovirus type 40/41 Clostridium difficile toxin Cyclospora cayetanesis Astrovirus Plesiomonas shigelloides Entamoeba histolytica/dispar Norovirus Salmonella species Giardia lamblia Rotavirus Yersinia enterocolitica grp. Sapovirus E.coli Shiga-like toxin Positive E.coli 0157 Shigella species Susceptibilities are performed and reported for Salmonella spp. and Shigella spp. 12

RPP (Respiratory Pathogen Panel) The RPP (Gastrointestinal Pathogen Panel) tests for 17 pathogens associated with infectious respiratory illness. Yield is similar if nasopharyngeal swabs or nasal washings are collected. Samples from Network of Care are sent to Children s Anschutz Campus for processing. Viruses Bacteria Rhinovirus/Enterovirus Parainfluenza 1-4 Mycoplasma pneumoniae Human Metapneumovirus RSV Chlamydophila pneumoniae Adenovirus Bordetella pertussis* Influenza A (and H1 and H3 subtypes) Influenza B (both clades detected) Coronaviruses (HKU1, NL63, OC43, 229E) *Bordetella pertussis is detected in the RPP panel, but must be confirmed by pertussis specific PCR. If concerned about pertussis, order Bordetella pertussis and Bordetella parapertussis specific PCR tests. BCID (Blood Culture Identification Panel) The BCID panel tests for 24 pathogens and 3 antibiotic resistance genes associated with bloodstream infections and is run automatically on all initial positive blood cultures. Gram Positive Bacteria Gram Negative Bacteria Yeast Enterococcus spp. Acinetobacter baumannii Candida albicans Listeria monocytogenes Haemophilus influenzae Candida glabrata Staphylococcus spp. Neisseria meningitidis Candida krusei Staphylococcus aureus Pseudomonas aeruginosa Candida parapsilosis Streptococcus spp. Enterobacteriaceae (Enteric bacteria) Candida tropicalis Streptococcus agalactiae Enterobacter cloacae complex Streptococcus pyogenes Streptococcus pneumoniae Esherichia coli Klebsiella oxytoca Klebsiella pneumoniae Proteus spp. Serratia marcescens Antibiotic Resistance Genes, if positive resistance is present: meca methicillin resistance vana/b vancomycin resistance associated with VRE KPC one type of carbapenem resistance associated with high level resistance in gram negatives Positive results are reported directly to Antimicrobial Stewardship from 8am-5pm, Monday-Friday and they relay the report to the clinician. On weekends, holidays and outside regular hours, the report is phoned directly to the clinician. 13

Culture Collection and Testing Information Blood Cultures If antibiotics will be started or changed, CHCO policy recommends collection of two blood cultures in advance. Separately prepare the IV caps when drawing from a central line. Place each blood specimen into a separate blood culture bottle. When followed correctly, this practice provides a better interpretation, as organisms detected in one of two culture are likely to be a normal skin flora contaminant. Select the type of bottle type based on the volume of blood to be drawn from the patient (Table 1). Collect at least 1 ml of blood with at an additional 1 ml of blood for each year of age to a maximum of 10 ml. Volumes of blood less than 1 ml are generally insufficient for the accurate exclusion of bacteremia. Although we never reject a blood culture, the volume of blood is critical (more is better). If collecting blood from patients with suspected endocarditis, 3 large volume blood cultures are best, up to 10mL. Table 1: Blood Culture Quantities by Age Age Minimum (ml) Blood Culture Bottle Per Each Blood Type Culture 0y (less than 1 y) 1 ml (Pink) BD Bactec Peds Plus 1 y 2 ml (Pink) BD Bactec Peds Plus 2 y 3 ml (Pink) BD Bactec Peds Plus 3 y 4 ml (Blue) BD Bactec Plus etc. etc. (Blue) BD Bactec Plus 9 y and older 10 ml (Blue) BD Bactec Plus Anaerobic blood cultures are infrequently utilized in pediatric patients due to the rare incidence of anaerobic bacteremia in our population. In cases of suspected Lemierre s disease or bacteremia due to deep wound infection or abscess, request an anaerobic blood culture bottle from the Microbiology Laboratory. Single isolates: Susceptibility testing automatically performed on isolates from any patient if blood obtained from peripheral line or from catheter of Bone Marrow Transplant and Hematology/Oncology patients. Multiple isolates recovered in succession: Susceptibility testing is performed automatically on the first two isolates from blood and CSF cultures. Susceptibilities are repeated on isolates obtained from positive cultures collected 4 days or more after the initial susceptibility test. The first three isolates are frozen for future reference. 14

Urine Cultures Catheter specimens are preferred. Always exclude the first drops. Avoid clean catch or bag specimens for culture if urinary tract infection (UTI) is likely; especially if antibiotics are to be started. Please refer to CHCO Clinical Care Guidelines for current recommendations for diagnosis of UTI. Clean Catch or Bag urine cultures are most helpful when they are negative. Be aware that colony counts may be < 100,000 cfu/ml in any age child with UTI if the specimen is not concentrated, and that children may have true UTI with multiple organisms. A urine specific gravity and nitrite test may help interpret results. For Catheter, Clean Catch or Bag specimens, susceptibilities are performed automatically on a single isolate with a colony count of 10,000 cfu/ml or greater; susceptibilities on mixed cultures must be requested. Urine for N. gonorrhoeae and C. trachomatis PCR should be from the first part of the stream without self-cleaning. Cotton ball samples are never appropriate for clinical practice. CSF Cultures Bacterial culture is performed on the first tube collected. Cell count is performed on tube #3. Susceptibility testing automatically performed for CSF shunt or lumbar puncture specimens. Tissues and Aspirates Tissues and aspirates (not swabs) are the preferred diagnostic specimens for wound and tissue infection. The quantity of specimen contained on a swab is usually insufficient for a good culture and does not permit a Gram stain to be performed. Swabs also retain >70% of the bacteria collected so cultures are compromised: Get fluid in a syringe if possible. For minute specimen volumes (may not be visible in the syringe), inoculate a blood culture bottle using the aspiration needle directly by rinsing the syringe contents through the aspiration needle into the bottle broth. Isolates recovered from swabs and other sources that are potentially contaminated with normal flora are only tested for susceptibilities when one or two recognized pathogens are recovered. Please see the Laboratory Test Directory for specific collection instructions for each test and swab type, if swab cannot be avoided. Anaerobic Tissue Cultures Isolation of anaerobes requires special collection and transport techniques. Please call Microbiology for appropriate media. Aspirates that are collected from a site that is adjacent to a mucous membrane are not appropriate for anaerobic culture due to the presence of normal anaerobic flora at these sites. Susceptibility testing for anaerobes is not available at Children s Hospital Colorado although most anaerobes have a predictable susceptibility pattern (see Table 7). Respiratory Cultures (Tracheal Aspirates) Susceptibilities are not routinely performed on isolates from tracheal aspirates. Susceptibilities will be performed on recognized pathogens when a single organism is seen on Gram stain with few or more polymorphonuclear cells or when a single or predominant organism grows in culture. TB Sputum and Quantiferon collection Collect sputum for TB testing early in the morning for three consecutive mornings. Blood for Quantiferon testing must be collected following special collection instructions per laboratory protocol. 15

Cystic Fibrosis Cultures Respiratory cultures from CF patients are a specific order. Upon isolation of glucose-non-fermenting gram negative rods including P. aeruginosa, susceptibilities by E-test method are performed for inpatients. Extended incubation times may be required for mucoid and slow growing CF isolates. MRSA Confirmation All S. aureus isolates are tested for vancomycin resistance. Detection of MRSA from a nasal swab indicates colonization but does not imply systemic colonization. PBP2A Latex Detection, ChromAgar, Microscan MIC, and cefoxitin screen are methods that the Microbiology Laboratory utilizes for MRSA confirmation depending on the source. HSV Testing Complete testing for neonatal HSV includes collection of surface swabs (eye, throat, and rectum) for HSV Culture, blood for HSV PCR, and CSF for MEP or HSV PCR. Collect lesion/ulcer specimens using special swabs and viral transport medium obtained from Microbiology. Unroof lesion if possible and send for HSV Direct Stain and Culture. If scab is present, collect whole scab in transport medium and order HSV PCR (culture is insensitive on old lesions). Call Microbiology if antiviral susceptibility testing is needed. VRE (Vancomycin Resistant Enterobacteriaceae) Confirmation Vancomycin resistance in Enterococcus spp. isolates is mediated by van genes that encode enzymes that modify the vancomycin binding target. Glycopeptide resistance in enterococci may be intrinsic or acquired. Intrinsic vancomycin resistance is encoded by the vanc gene, which is found chromosomally in Enterococcus gallinarum and Enterococcus casseliflavus. Intrinsic resistance typically produces MICs of 2 32 ug/ml for vancomycin, and these organisms are generally susceptible to ampicillin. Organisms that display this low level intrinsic resistance mechanism are not particularly concerning from an infection control standpoint and they are not considered to be vancomycin resistant enterococci (VRE). Acquired vancomycin resistance is encoded by the vana and vanb genes and is found in E. faecalis, E. faecium, and rarely in E. durans. Strains that harbor the vana gene have high levels of resistance to vancomycin and teicoplanin, whereas strains that harbor the vanb gene have variable levels of resistance to vancomycin only. These organisms are true VRE and are an infection control concern because the genes are transmitted between organisms on plasmids. This type of resistance is associated with increased morbidity and mortality, particularly in immune-compromised patients. Enterococcus spp. isolates that test resistant or intermediate to vancomycin by Microscan panel are reidentified using Maldi-TOF. MICs to vancomycin are confirmed using the E-test method. 16

CRE (Carbapenem Resistant Enterobacteriaceae) Confirmation CRE are enteric Gram negative rods that are carbapenem resistant. Different molecular mechanisms can determine carbapenem resistance: 1. Production of a carbapenemase. 2. Production of an extended-spectrum Beta-lactamase (ESBL) and/or an AmpC Beta-lactamase in conjunction with membrane impermeability or active drug efflux. All enteric Gram negative rods that are tested for susceptibilities are screened for carbapenem resistance. Ertapenem, imipenem, and meropenem with MICs in the intermediate or resistant range are submitted to the CDPHE (Colorado Department of Health and Epidemiology) for screening and confirmed for the production of carbapenemases by molecular methods as needed. Consult with Epidemiology/Infection Control, Antimicrobial Stewardship and Infectious Disease for isolation and treatment of these patients. Antimicrobial Susceptibility Testing Susceptibility testing is performed on significant isolates from the first positive culture from any source. Additional positive cultures are referred to the first culture on the same or similar source for three days. Organisms recovered four or more days later will be retested. MRSA, VRE and all isolates recovered from blood, CSF, brain tissue or aspirate are frozen for future reference. All other isolates are saved for 7 days before they are discarded. Susceptibility testing, an important function of the Microbiology Laboratory, is expensive, time consuming and not required for all isolates. Organisms that have predictable susceptibility patterns do not require such testing and fastidious isolates may yield results that are difficult to interpret. Multiple testing methods are utilized because all methods are not suitable for all isolates. The Microbiology Laboratory has established protocols for testing and reporting of bacterial isolates commonly encountered at CHCO to provide healthcare providers with reliable results. E-test MIC, Microscan MIC, Kirby Bauer Disk, PBP2A, D-test and Beta-lactamase are all methods utilized to predict an organism s antimicrobial susceptibility. CHCO adheres to Clinical and Laboratory Standards Institute (CLSI) guidelines for susceptibility testing and MICs are interpreted as susceptible, intermediate and resistant per these guidelines. When choosing a drug for the treatment of an infection, the site of infection and drug penetration to the site of infection must be considered. The pharmacists or antimicrobial stewards should be consulted to answer questions regarding pharmacokinetics and pharmacodynamics of drug-bug interactions. Culture Results Check the computer for culture status and updated reports. If results are pending, the culture has not been read or does not meet the criteria for a negative report (i.e. not incubated long enough). Most negative reports are not issued before 18-24 hours. Network of Care Urgent Values are reported by Epic Inbox. 17

Critical and Urgent Value Reporting Policy for Microbiology Critical Values- The following critical results are phoned directly to the patient s licensed caregiver within 30 minutes for inpatients and within 60 minutes for outpatients: 1. Positive blood culture Gram stain report (first positive) 2. Positive CSF Gram stain report (first positive) 3. Positive CSF culture report (first positive) 4. Positive HSV PCR on CSF, blood or swab specimen from a neonate (first positive) 5. MEP positive for bacteria, Cryptococcus, HSV or VZV (first positive) 6. HSV Direct Stain or culture positive swab specimen from a neonate (first positive) 7. Positive Pneumocystis stain Urgent Values- The following results are called to the patient s licensed caregiver or nurse within 8 hours for inpatients or the next business day for outpatients (first positive stain, culture or PCR): 1. Blood or CSF culture definitive identification of isolate, including results of BCID 2. Subsequent CSF or Blood culture positives in a series 3. MEP positive for CMV, HHV6, enterovirus or parechovirus. 4. Single organism isolated from a tissue, aspirate or surgical site 5. Methicillin Resistant Staphylococcus aureus (MRSA) by culture or PCR (first positive) 6. Penicillin resistant Streptococcus pneumoniae 7. Vancomycin resistant Enterococcus faecalis, Enterococcus faecium, Enterococcus durans (VRE) 8. Drug Resistant Organism 9. Group A streptococcus throat or rectal (Network of Care and ED obtain reports via Epic In-box) 10. Group A streptococcus from non-throat or non-rectal sources are called to all sites 11. Fusobacterium spp. isolated from any site 12. GIP positive for Salmonella spp or, Shigella spp.in patients less than 6 months of age. 13. GIP positive for E. coli 0157 or positive shiga-toxin. 14. Legionella spp. isolated from any culture 15. Fungal mold isolates except CF sputa and dermatophytes 16. Mycobacterium spp. a. Positive stain for Acid-Fast Bacilli (AFB) b. Mycobacterium spp., first positive culture c. Mycobacterium tuberculosis 17. Positive test for syphilis (first positive) 18. Positive C. difficile PCR 19. Positive N. gonorrhoeae or Chlamydia trachomatis PCR with confirmation requested or from a CHIP patient. 20. Positive B. pertussis or B. parapertussis PCR 21. Positive Enterovirus PCR 22. Positive Parechovirus PCR 23. First positive CMV, EBV, Adenovirus, or HHV6 PCR 24. HSV PCR (non-csf or Blood) (subsequent positives) 25. HSV or CMV detected by any method on any source on neonates <2 months old 26. Influenza virus detected by any test (Network of Care and ED obtain reports via Epic In-box) 18

Fungus Bacteria - Aerobic Gram - Bacteria - Aerobic Gram + 2016 Predominant Blood Isolates Bacillus 9 Beta Strep Group A 10 Beta Strep Group B 5 Enterococcus faecalis 24 Enterococcus faecium 3 MRSA 8 MSSA 53 Staphylococcus coag. neg. 56 Strep anginosus 8 Strep pneumoniae 15 Viridans strep 30 Enterobacter cloacae 15 Escherichia coli 20 Haemophilus influenzae 6 Klebsiella ocytoca 11 Klebsiella pneumoniae 10 Salmonella 4 Pseudomonas aeruginosa 10 Candida albicans 3 Candida parapsilosis 3 0 20 40 60 19

MRSA and VRE Rates 20

All other sources Stool Surveillance 21 7 Vancomycin Resistant Enterococcus spp. First time Isolations 6 5 4 3 2 1 0 2008 2009 2010 2011 2012 2013 2014 2015 2016

Influenza Virus Treatment The viral neuraminidase inhibitors osteltamivir (Tamiflu ) is an FDA approved antiviral medication currently available for the treatment or prophylaxis of influenza virus infections of children. Peramivir (Rapivab ) is a similar medication licensed only for treatment of patients 18 years old and older. The neuraminidase inhibitors are active against influenza A and influenza B viruses. In the 2016-17 influenza season, almost all characterized influenza virus isolates were sensitive in vitro to these medications. When started within the first two days of onset of influenza illness, oseltamivir can reduce illness severity and shorten the duration of fever and symptoms of uncomplicated influenza by an average of 1-2 days in healthy outpatients. These medications may also reduce the risk of serious influenzarelated complications (e.g., pneumonia, respiratory failure, exacerbation of chronic diseases and death). When clinically indicated, oseltamivir should be started as soon as possible after symptom onset, ideally within 48 hours of symptom onset. Treatment should not wait for laboratory confirmation of influenza. Many experts would start antiviral treatment for any child ill enough to be hospitalized with a clinical diagnosis of influenza. Treatment started 4-5 days after symptom onset may still be beneficial in preventing influenza-related complications and deaths in patients at high risk of such complication or with severe or progressive influenza. Duration of Treatment or Chemoprophylaxis Treatment Recommended duration for antiviral treatment is 5 days. Longer treatment courses for patients who remain severely ill after 5 days of treatment can be considered. Chemoprophylaxis Recommended duration is 7 days after exposure. For control of outbreaks in long-term care facilities and hospitals, CDC recommends antiviral chemoprophylaxis for a minimum of 2 weeks, included vaccinated persons, and up to 1 week after the last known case was identified. 22

23 Antiviral agent Oseltamivir (Tamiflu ) Antiviral Medications Recommended for Treatment and Chemoprophylaxis of Influenza, 2015 2016 Influenza Season FDA Not Use approved recommended for for use in Activity against Influenza A and B Treatment Chemoprophylaxis 1 year and older 3 months and older None Children Adults Adverse events FDA approved for treatment in children of any age. If < 1 yr old, the dose is 3 mg/kg/dose twice daily. If > 1 yr old and weight 15 kg or less, the dose is 30 mg twice a day; weight > 15 to 23 kg, the dose is 45 mg twice a day; weight > 23 to 40 kg, the dose is 60 mg twice a day; more than 40 kg, the dose is 75 mg twice a day. If child is < 3 months old, chemoprophylactic use is not recommended unless situation is judged critical because of limited data on use in the age group. If child is 3 months - 1 year, dose is 3 mg/kg once daily. Greater than 1 yr: weight 15 kg or less, the dose is 30 mg once daily; weight > 15 to 23 kg, the dose is 45 mg once daily; weight > 23 to 40 kg, the dose is 60 mg once daily; more than 40 kg, the dose is 75 mg once daily. 75 mg twice daily 75 mg once daily Adverse events: nausea, vomiting. Transient neuropsychiatric events (self-injury or delirium) mainly reported among Japanese adolescents and adults.

24 Antiviral agent Peramivir (Rapivab ) Zanamivir* (Relenza ) *Not on CHCO formulary Antiviral Medications Recommended for Treatment and Chemoprophylaxis of Influenza, 2015 2016 Influenza Season FDA Not Activity Use approved recommended against for for use in Influenza A and B Influenza A and B Treatment Treatment Chemoprophylaxis Adult (18 years and older) 7 years and older 5 years and older People with underlying respiratory disease (e.g. asthma, COPD) Children Adults Adverse events (Not FDA approved for use in children <18 years of age due to limited data in this age group.) Birth 3 months, 6 10 mg/kg IV once daily; greater than 3 months 17 years, 10 mg/kg IV once daily 10 mg (2 inhalations) twice daily (Not FDA approved for use in children < 7 years old) 10 mg (2 inhalations) once daily (Not FDA approved for use in children < 5 years old) 600 mg IV once daily 10 mg (2 inhalations) twice daily 10 mg (2 inhalations) once daily Diarrhea, vomiting, neutropenia Allergic reactions: oropharyngeal or facial edema. Adverse events: diarrhea, nausea, sinusitis, nasal signs and symptoms, bronchitis, cough, headache, dizziness, and ear, nose and throat infections.

Guidelines for Changing from IV to PO Antibiotics in Hospitalized Children Over 2 Months of Age at Children s Hospital Colorado CONSIDERATIONS / BASIC PRINCIPLES: Advantages of an IV to PO conversion are to provide an oral or enteral dosage form with comparable bioavailability to the intravenous form. This could reduce hospital length of stay and will avoid added risks associated with continued intravenous therapy. This will lower the overall medication and associated costs to the patient and the hospital. PROTOCOL: 1) Antimicrobial Therapy a) The following antimicrobials have an oral analogue with greater than or equal to 90% bioavailability and may be switched at or after initiation of treatment: i) Antimicrobials Rifampin Metronidazole Levofloxacin / ciprofloxacin* Clindamycin Linezolid Fluconazole Voriconazole Bactrim (sulfamethoxazole / trimethoprim) [dose based on trimethoprim] * ciprofloxacin is 80% bioavailable ii) Recommend changing from IV to PO if: 1) Clinically stable 2) Tolerating enteral nutrition by the oral, gastric, or other appropriate enteral tube 3) Tolerating other medications by the oral route 4) Medical and social situation will allow patient to comply with oral antibiotic therapy once discharged from the hospital iii) Consider continuing IV therapy if: 1) NPO including medications 2) Unable to tolerate oral formulation 3) Presence of vomiting or diarrhea in the previous 24 hours, gastrointestinal obstruction, malabsorption syndrome, or ileus 4) Antimicrobial being used for bacteremia/line infection 5) Conversion to oral dose of clindamycin greater than 1.8 gm/day 6) Receiving continuous enteral feeds that cannot be interrupted and the antibiotic must be given on an empty stomach 7) Severe Sepsis (with organ dysfunction) 8) CNS Infection, endovascular infection 9) Fever and Neutropenia 25

b) Changing from IV to PO when there is LESS THAN 90% bioavailability. The following related antimicrobial alternatives* may be switched after initial intravenous therapy once the patient has met the following inclusion criteria and does not meet the following exclusion criteria: i) Recommend changing from IV to PO if: 1) Clinically stable 2) Tolerating enteral nutrition by the oral, gastric, or other appropriate enteral route 3) Tolerating other medications by the oral route 4) Signs, symptoms (fever, pain) and indicators of infection (CBC, ESR, CRP) have resolved or are improving 5) Medical and social situation will allow patient to comply with oral antibiotic therapy once discharged from the hospital ii) Consider continuing IV therapy under the following circumstances: 1) NPO including medications 2) Unable to tolerate oral formulation 3) Presence of vomiting or diarrhea in the previous 24 hours, gastrointestinal obstruction, malabsorption syndrome, or ileus 4) Antimicrobial being used for bacteremia/line infection 5) Receiving continuous enteral feeds that cannot be interrupted and the antibiotic must be given on an empty stomach 6) Severe Sepsis (with organ dysfunction) 7) CNS infection or endovascular infection 8) Fever and Neutropenia Intravenous Antibiotic Oral Alternative* Cefotaxime, ceftriaxone ** Ampicillin Amoxicillin Ampicillin / sulbactam Amoxicillin / clavulanic acid Cefazolin Cephalexin * Bacterial infections with a known organism and susceptibilities can help guide choosing a well absorbed unrelated alternative. ** Oral 3 rd gen cephalosporins (i.e. cefdinir) are not well absorbed and do not provide adequate step down therapy. Recommend oral amoxicillin or amoxicillin/clavulanate if sensitive. For PCN allergic, may use cefuroxime or cefpodoxime; cefdinir has inferior serum levels. 26

27 Antimicrobial Formulations at Children s Hospital Colorado Children s Hospital Colorado Antimicrobial Formulary June 1, 2016 IV Oral Monitor DOSE Information Antimicrobial Levels IV Cost Oral Cost Adjust for Food Bioavailability (Oral Alternatives)** Antivirals ACYCLOVIR $$$ $ w/wo 10-20% R HSV encephalitis: 3 months or less, 20 mg/kg/dose q8h; 4 mos or greater, 10 mg/kg/dose qh8 CIDOFOVIR $$$$$ R 5 mg/kg/dose Q1-2 weeks; must be given with probenacid FOSCARNET $$$$ R CMV Treatment: 60 mg/kg/dose q8h or 90 mg/kg/dose q12h Maintenance: 90 120 GANICICLOVIR $$$ $$$ w 6 9% R, CBC IV mg/kg/dose q24h CMV prophylaxis: 5 mg/kg/dose q24h CMV treatment: 5 mg/kg/dose q12h Neonatal CMV treatment: 6 mg/kg/dose q12h * refer to specific transplant protocol for dosing PO Suppressive therapy for recurrent herpes: 20 mg/kg/dose TID; Varicella tx: 20 mg/kg/dose QID; Herpes Zoster tx: 20 mg/kg/dose 5 times daily (max 800 mg/dose). 200 mg caps; 400, 800 mg tabs; 200 mg/6 ml susp Level done at: Turnaround time Mayo 5 9 days Not offered Focus 5 6 days Normal Levels Peak: 0.40 2.0 mcg/ml plasma Trough: 0.14 1.2 mcg/ml plasma Peak Serum Level (PO; 1000 mg dose) 1.2 mcg/ml Peak Serum Level (IV; 5 mg/kg/dose) 8.3 mcg/ml

28 Antimicrobial Formulations at Children s Hospital Colorado Antifungals AMPHOTERICIN B AMPHOTERICIN B LIPOSOME IV Oral Monitor DOSE Information Antimicrobial Levels IV Cost Oral Cost Adjust for Food Bioavailability (Oral Alternatives)** IV PO Level done at: $$ See Azoles R, L 0.5 1 mg/kg/day q24h Univ of TX $$$$$ See Azoles R, L 3 5 mg/kg/day q24h, may use 7.5 mg/kg/dose for lung infections, doses as high as 10 mg/kg/dose q24h have been used for CNS infections FLUCONAZOLE $$ $ $$ w/wo 90% R, L Prophylaxis/oral thrush/urinary tract: 3 mg/kg/day; Oral candidiasis: 3 6 mg/kg/day; Candidemia: 6 12 mg/kg/day; Esophogeal invasive disease:(endocarditis/cn S/endophthalmitis, etc): 10 12 mg/kg/day; Systemic: 6 12 mg/kg/day (all q24h dosing) Prophylaxis/oral thrush/urinary tract: 3 mg/kg/day Oral candidiasis: 3 6 mg/kg/day; Candidemia: 6 12 mg/kg/day; Esophogeal invasive disease: (endocarditis/ CNS/ endophthalmitis, etc.): 10 12 mg/kg/day; Systemic: 6 12 mg/kg/day (all q24h dosing); 25, 50, 100, 150, 200 mg tabs; 40 mg/ml susp Turnaround time 5 days Normal Levels Mayo 7days 4.0 20 mcg/ml ITRACONAZOLE $$$ w(caps) wo(soln) 55% L, TDM 3 10 mg/kg/day; 100 mg caps; 10 mg/ml sol Mayo 3 days Trough: > 0.5 mcg/ml (localized infection) > 1 mcg/ml (systemic infection)

29 Antimicrobial Formulations at Children s Hospital Colorado IV Oral Monitor DOSE Information Antimicrobial Levels IV Cost Oral Cost Adjust for Food Bioavailability (Oral Alternatives)** MICAFUNGIN $$$$ See Azoles R, L, CBC, TDM VORICONAZOLE $$$$$ $$$$ $$$$$ POSACONAZOLE $$$$$ $$$$ $$$$$ wo 96% R, L, CBC, TDM Liquid with food Liquid (variable) Tablet (54-70%) R, L, CBC, TDM IV Prophylaxis: 2 mg/kg/day q24h (max 50 mg/dose); Treatment: less than 6 mos: 8 10 mg/kg/day; 6 mos 6 yrs: 4 mg/kg/day; 6 16 yrs: 3 mg/kg/day; q24h Adult: 12 mg/kg/day divided q12h x 2 doses then 8 mg/kg/day divided q12h Neonate: 12 20 mg/kg/day divided q8 12h Less than 2 yrs: 18 mg/kg/day divided q12h Greater than 2 yrs: 18 mg/kg/day divided q12h 50, 100, 200 mg tabs; 40 mg/ml susp Adult: 300 mg IV q24h Children: 7 10 mg/kg/day has been used PO 12 years and older: > 40kg 200 300 mg PO BID Neonate: 12 20 mg/kg/day divided q12h Greater than 2 years: 18 mg/kg/day divided q12h 50, 100, 200 mg tabs; 40 mg/ml susp 100 mg DR tab: Adult 300 mg po qd 40 mg/ml Liquid: Adult 400 mg BID or 200 mg QID Children 12 20 mg/kg/day divided QID has been used Level done at: Univ of TX Turnaround time 2 7 days Mayo 2-4 days Normal Levels Suggested: trough greater than 1 mcg/ml (higher levels may be required) Mayo Trough Therapeutic Range: 1.0 5.5 mcg/ml Mayo 7 days Suggest trough greater than 0.7 mcg/ml (higher levels may be required)

2 hours (STAT 35 minutes) draw Refer to CHCO formulary depends on timing of the draw Refer to CHCO formulary depends on timing of the draw 30 Antimicrobial Formulations at Children s Hospital Colorado IV Oral Monitor DOSE Information Antimicrobial Levels IV Cost Oral Cost Adjust for Food Bioavailability (Oral Alternatives)** Antibiotics Aminoglycosides AMIKACIN $$ Check Susceptibilities R, TDM IV PO Level done at: Turnaround time 7.5 mg/kg/dose q8h UCHSC Run Daily Normal Levels Refer to CHCO formulary depends on timing of the GENTAMICIN $ Check Susceptibilities R, TDM Neonates: see formulary; Children: 2.5 mg/kg/dose q8h CHCO TOBRAMYCIN $$ Check Susceptibilities R, TDM 2.5 mg/kg/dose q8h CHCO 2 hours (STAT 35 minutes) Penicillins AMOXICILLIN (preferred regimen for CAP) $ w/wo 89% R AOM: 90 mg/kg/day divided BID; CAP:90 mg/kg/day divided TID; UTI: 25-50 mg/kg/day divided TID; Strep throat:25-50 mg/kg/day divided BID; 250, 500 mg caps; 250, 400 chewable; 875 mg tab Focus 6 days

31 Antimicrobial Formulations at Children s Hospital Colorado AMOXICILLIN- CLAVULANATE AMPICILLIN (preferred regimen for CAP) AMPICILLIN- SULBACTAM IV Oral Monitor DOSE Information Antimicrobial Levels IV Cost Oral Cost Adjust for Food Bioavailability (Oral Alternatives)** $$ w/wo 89% R High dose formulation: CAP: 90 mg/kg/day divided TID, AOM: 90 mg/kg/day divided BID; 600-42.9 mg/5 ml susp, 875-125 mg tabs Regular formulation: UTI: 25-50 mg/kg/day divided TID 200-28.5, 250-62.5, 400-57 ml chewable; 400-57 ml susp; 250-125, 500-125 tabs $$$ $ Wo 50% R UTI: 100 200 mg/kg/day divided q6h Bacteremia/CAP/SSTI: 200 mg/kg/day divided q6h Meningitis: 200 400 mg/kg/day divided q6h (max 2 gm/dose) $$$ See Amox/ Clav NAFCILLIN $$$ See Cephale x in Diclox Check Susceptibilities Check Susceptibilities R R, CBC, UA IV UTI: 100 200 mg/kg/day divided q6h Bacteremia/CAP/SSTI: 200 mg/kg/day divided q6h Meningitis: 200 400 mg/kg/day divided q4 6h (max 2gm/dose) Moderate infection: 50 100 mg/kg/day divided q6h Severe: 100 200 mg/kg/day divided q4 6h (max dose 2 gm/dose) Can infuse as continuous infusion (200 mg/kg/day max 10gm) PO 50 100 mg/kg/day (max 3 gm/day) divided QID; 250, 500 mg caps; 250 mg/5 ml susp Level done at: Turnaround time Focus 6 days Focus 6 days Focus 6 days Normal Levels

32 Antimicrobial Formulations at Children s Hospital Colorado PENICILLIN G Potassium PENICILLIN G BENZATHINE 600000 UNIT/ML IM SUSP (For IM Administration Only) PENICILLIN V POTASSIUM PIPERACILLIN- TAZOBACTAM IV Oral Monitor DOSE Information Antimicrobial Levels IV Cost Oral Cost $ See Pen V $$$ See Pen V Adjust for Food Bioavailability (Oral Alternatives)** IV R 100,000 to 250,000 units/kg/24 hours in divided doses every 4 6 hours; Severe infections: Up to 400,000 units/kg/24 hours in divided doses ever 4 6 hours (max dose 24 million units/24 hours) R (For IM Administration ONLY) Group A streptococcal upper respiratory infection: 25,000 units/kg as a single dose; maximum 1.2 million units; Prophylaxis of recurrent rheumatic fever: 25,000 units/kg every 3 4 weeks; maximum: 1.2 million units per dose; Early syphilis: 50,000 units/kg as a single injection; maximum 2.4 million units; Syphilis of more than 1-year duration: 50,000 units/kg every week for 3 doses; maximum: 2.4 million units per dose $ wo 25 60% R 25 50 mg/kg/24 hrs divided every 6 8 hrs (max 500 mg/dose); 125, 250, 500 mg tabs; 250 mg/5 ml susp $$$$$ Check Susceptibilities R, L Dose based on piperacillin: 240 400 mg/kg/day (max 4 gm/dose) divided 6-8 hrs PO Level done at: Turnaround time Focus 6 days Focus 6 days Focus 6 days Focus 6 days Normal Levels

33 Antimicrobial Formulations at Children s Hospital Colorado Cephalosporins First Generation CEFAZOLIN SODIUM IV Oral Monitor DOSE Information Antimicrobial Levels IV Cost Oral Cost $$ See Cephalexin Diclox Adjust for Food Bioavailability (Oral Alternatives)** Check Susceptibilities R IV 50 150 mg/kg/day divided q6-8h (max 2 gm/dose, 6 gm/day) CEPHALEXIN $ w/wo 90% R 25-50 mg/kg/day divided QID; osteo: 100-150 divided QID (max 1gm/dose); 250, 500 mg caps; 250 mg/5 ml susp Second Generation CEFOXITIN $$$ R Neonates: 90 100 mg/kg/day divided q8h Children: 160 mg/kg/day divided q4 6h (max 2 gm/dose) CEFUROXIME SODIUM $$$ $$ w/wo (tabs) w(susp ) Third Generation CEFOTAXIME $$$ Check Susceptibilities CEFTRIAXONE $$ Check Susceptibilities 37 52% R 75-150 mg/kg/day divided q8h (max 2 gm/dose) R 100 200 mg/kg/day divided q6 8h Meningitis: 200 300 mg/kg/day divided q6 (max 2 gm/dose) 50 75 mg/kg/day divided q12 24 Meningitis and osteo: 100 mg/kg/day divided q12 24h (max 2 gm/dose) PO 20 30 mg/kg/day divided BID (max 500 mg/dose); 62.5, 125, 250, 500 mg tab; 125 mg/5 ml susp Level done at: Turnaround time Focus 6 days Focus or Seattle 6 days Run daily Focus 6 days Focus 6 days Focus 6 days Normal Levels

34 Antimicrobial Formulations at Children s Hospital Colorado IV Oral Monitor DOSE Information Antimicrobial Levels IV Cost Oral Cost Adjust for Food Bioavailability (Oral Alternatives)** CEFIXIME $$$ w/wo 40 50% R 8 mg/kg/day in 1 2 divided doses (max 400 mg/day); 100, 200, 400 mg tabs; 100 mg/5 ml susp CEFTAZIDIME $$$ Check Susceptibilities Fourth Generation CEFEPIME HCL INJ $$$ Check Susceptibilities Carbapenems MEROPENEM $$$ Check Susceptibilities R R R, L, CBC IV 100 150 mg/kg/day divided q8h (max 2 gm/dose) 100 mg/kg/day divided q12h; F&N and serious infections: 150 mg/kg/day divided q8h (max 2 gm/dose) Moderate infection: 60 mg/kg/day divided q8h (max 1 gm/dose); Meningitis: 120 mg/kg/day divided q8h (max 2gm/dose) Macrolide/Azalides AZITHROMYCIN $ w/wo 38% 10 mg/kg/day q24h (max 500 mg) PO 10 mg/kg/day, day 1 (max 500 mg), then 5 mg/kg/day (max 250 mg); Campylobacter and shigellosis: 10 mg/kg/day x 3 days 125, 250 mg tabs; 200 mg/5 ml susp Level done at: Turnaround time Focus 6 days Focus 6 days NJH 2 7 days Normal Levels

35 Antimicrobial Formulations at Children s Hospital Colorado CLARITHROMYCI N ERYTHROMYCIN BASE ERYTHROMYCIN LACTOBIONATE Quinolones CIPROFLOXACIN (do not give suspension via g-tube) IV Oral Monitor DOSE Information Antimicrobial Levels IV Cost Oral Cost $$$ See above $$ $ (tab) $$ (susp) Adjust for Food Bioavailability (Oral Alternatives)** $$ w/wo 50% R, L 15 mg/kg/day divided BID, for MAC 30 mg/kg/day divided BID have been used; 125, 250, 500 mg tab; 250 mg/5 ml susp $ $$ wo 18 45% R, L 30 50 mg/kg/day divided QID (max 500 mg/dose); 250, 333, 500 mg tabs; 200, 400 mg E.E.S. tabs; 200 w/wo; avoid taking with Ca, Mg, Zn, Al, Fe LEVOFLOXACIN $$$ $$$ w/wo; avoid taking with Ca, Mg, Zn, Al, Fe IV R, L 20 40 mg/kg/day divided q6h (max 1 gm/dose) 80% R 15 20 mg/kg/day divided q12; Severe infection: 30 mg/kg/day divided q8h (max 400 mg/dose) 98% R, L Children less than 5 years: 20 mg/kg/day divided q12h; 5-10 yrs: 15 mg/kg/day divided Q12h for serious infections; 10 yrs and greater: 10 mg/kg/day q24h (normal 500 mg/dose; max for severe infection: 750 mg/dose) PO mg/5 ml susp 20 30 mg/kg/day divided BID (max 750 mg/kg/dose); CF: 40 mg/kg/day divided BID (max 1gm/dose); 125, 250, 500, 750 mg tab; 500 mg/5 ml susp Children less than 5 years: 20 mg/kg/day divided q12h; 5-10 yrs: 15 mg/kg/day divided q12h for serious infections; 10 yrs and greater: 10 mg/kg/day q24h (normal 500 mg/dose; max for severe infection: 750 mg/dose); 62.5, 125, 250, 500 mg tabs; 25mg/mL sol Level done at: Turnaround time NJH 2 7 days Focus 6 days Focus 6 days NJH 2 7 days NJH 2 7 days Normal Levels

36 Antimicrobial Formulations at Children s Hospital Colorado Tetracyclines DOXYCYCLINE HYCLATE IV Oral Monitor DOSE Information Antimicrobial Levels IV Cost Oral Cost Adjust for Food $$ $$ wo; avoid taking with Ca, Mg, Zn, Al, Fe Bioavailability (Oral Alternatives)** Miscellaneous AZTREONAM $$$$$ Check Susceptibilities CLINDAMYCIN $$$ $ (cap) $$$$ (susp) > 90% 2 4 mg/kg/day in 1 2 divided doses (max 200 mg/day) R IV 150 mg/kg/day divided q8h; CF: 200 mg/kg/day divided q6h (max 2 gm dose) 90% 30 40 mg/kg/day divided q6 8h (max 4.8 gm/day) LINEZOLID $$$$$ $$$$ w/wo 100% CBC Children less than 12 yrs: 30 mg/kg/day divided q8h; 12 yrs and greater: 20 mg/kg/day divided q12h (max 600 mg/dose); Do not administer with MAOI s METRONIDAZOL E $$ $ w/wo 100% R, L, CBC 30 50 mg/kg/day divided TID QID (max 1000 mg/dose); 30 mg/kg/dose q25h for appendicitis RIFAMPIN $$$$ $$$ wo 95% L 10 20 mg/kg/day divided QD BID (max 600 mg/dose) PO 2 4 mg/kg/day in 1 2 divided doses (max 200 mg/day); 20, 50, 100 mg caps 30 40 mg/kg/day divided TID QID (max 1.8 gm/day); 75, 150, 300 mg caps; 75 mg/5 ml sol Children less than 5 yrs: 30 mg/kg/day divided TID; 5 yrs and greater: 20 mg/kg/day divided BID (max 600 mg/dose); 300, 600 mg tabs; 100 mg/5 ml susp 30 50 mg/kg/day divided TID QID (max 1000 mg/dose); 62.5, 125, 250, 500 mg tabs; 50 mg/ml susp 10 20 mg/kg/day divided QD BID (max 600 mg/dose); 150, 300 mg caps; 50 mg/ml susp Level done at: Turnaround time Focus 6 days Focus 6 days NJH 2 7 days Focus 6 days NJH 2 7 days Normal Levels

37 Antimicrobial Formulations at Children s Hospital Colorado SULFAMETHOXAZOLE- TRIMETHOPRIM IV Oral Monitor DOSE Information Antimicrobial Levels IV Cost $$ $$$ Oral Cost VANCOMYCIN $$$ $$ (soln) $$$$$ (cap) Adjust for Food Bioavailability (Oral Alternatives)** $ w/wo 90 100% R, L, CBC 0% Check Susceptibilities R, TDM IV Minor infection: 6 10 mg/kg/day divided q12h; Serious infection: 15 20 mg/kg/day divided q6h 15 20 mg/kg/dose q6 12h 40-50 mg/kg/day as a continuous infusion PO Minor infection: 6 10 mg/kg/day divided q12h; Serious infection: 15 20 mg/kg/day divided q6h; 100-20, 200-40, 400-80(ss), 800-160(ds) mg tabs; 200-40 mg/5 ml susp 10 mg/kg/dose q6h (max 125 mg/dose); 125mg; Level done at: Turnaround time Normal Levels Mayo 5 days > 50 mcg/ml CHCO 2 hours (STAT 35 minutes) 50 mg/ml sol **See Guidelines for Changing from IV to PO Antibiotics on page 24: Oral medication with 80% or greater bioavailability can obtain equal concentrations as IV formulations. R = adjust for renal impairment L = adjust for liver impairment TDM = Therapeutic Drug Monitoring MAOI = Monoamine oxidase inhibitor

38 Collection Guidelines for Antimicrobial Levels Test name Amikacin Peak EPIC code Specimen required L2918 Minimum 0.7 ml in a red or gold top tube Turnaround time Collection instructions 4 hours Peak should be drawn 30 minutes after end of infusion. Time of last Dose and Dosage is required for interpretation. Interpretation of results Therapeutic Range: 20 35 mcg/ml Urgent Values: > 35 mcg/ml will be phoned to a responsible caregiver Amikacin Trough Amikacin Random Gentamicin Peak Gentamicin Trough L2915 Minimum 0.7 ml in a red or gold top tube L2920 Minimum 0.7 ml in a red or gold top tube L1791 Minimum 0.4 ml in a green, gold, purple or red top tube L1789 Minimum 0.4 ml in a green, gold, purple or red top tube 4 hours Trough should be drawn 15 minutes prior to next dose. Time of last Dose and Dosage is required for interpretation. 4 hours 2 hours STAT 35 min Send STAT levels in a green or purple top 2 hours STAT 35 min Send STAT levels in a green or purple top Peak should be drawn 30 minutes after end of infusion. Time of last Dose and Dosage is required for interpretation. Trough should be drawn 15 minutes prior to next dose. Time of last Dose and Dosage is required for interpretation. Therapeutic Range: Less than 8 mcg/ml Urgent Values: > 10 mcg/ml will be phoned to a responsible caregiver Therapeutic Range: 5 12 mcg/ml Urgent Values: > 12 mcg/ml will be phoned to a responsible caregiver Therapeutic Range: Less than 2 mcg/ml Urgent Values: > 2.0 mcg/ml will be phoned to a responsible caregiver

39 Test name Gentamicin Random Tobramycin Peak Tobramycin Trough Tobramycin Random Vancomycin Peak Vancomycin Trough EPIC code Specimen required L1793 Minimum 0.4 ml in a green, gold, purple or red top tube L1799 Minimum 0.4 ml in a green, gold, purple or red top tube L1797 Minimum 0.4 ml in a green, gold, purple or red top tube L1801 Minimum 0.4 ml in a green, purple or red top tube L1807 Minimum 0.4 ml in a purple, red, or gold top tube NO GREEN TOP TUBES L1805 Minimum 0.4 ml in a purple, red, or gold top tube NO GREEN TOP TUBES Turnaround time 2 hours STAT 35 min Send STAT levels in green or purple top 2 hours STAT 35 min Send STAT levels in green or purple top 2 hours STAT 35 min Send STAT levels in green or purple top 2 hours STAT 35 min Send STAT levels in green or purple top 2 hours STAT 35 min Send STAT levels in purple top 2 hours STAT 35 min Send STAT levels in purple top Collection instructions Peak should be drawn 30 minutes after end of infusion. Time of last Dose and Dosage is required for interpretation. Trough should be drawn 15 minutes prior to next dose. Time of last Dose and Dosage is required for interpretation. Peak should be drawn 60 minutes after end of infusion. Time of last Dose and Dosage is required for interpretation. Trough should be drawn 15 minutes prior to next dose. Time of last Dose and Dosage is required for interpretation. Interpretation of results Therapeutic Range: 5 12 mcg/ml Urgent Values: > 12 mcg/ml will be phoned to a responsible caregiver Therapeutic Range: Less than 2 mcg/ml Urgent Values: > 2.0 mcg/ml will be phoned to a responsible caregiver Therapeutic range: 20 40 mcg/ml Urgent Values: > 45 mcg/ml will be phoned to a responsible caregiver Therapeutic Range: 5 20 mcg/ml Urgent Values: > 20.0 mcg/ml will be phoned to a responsible caregiver

40 Test name Vancomycin Random Vancomycin Continuous Infusion EPIC code Specimen required L1809 Minimum 0.4 ml in a purple, red, or gold top tube NO GREEN TOP TUBES L5860 Minimum 0.4 ml in a purple, red, or gold top tube NO GREEN TOP TUBES Turnaround time 2 hours STAT 35 min Send STAT levels in purple top 2 hours STAT 35 min Send STAT levels in purple top Collection instructions Recommend drawing level 24 hours after start or change in infusion rate. To prevent contamination: Do not draw level off of same line vanco is infusing, if vanco is infusing via peripheral line then level should be drawn from different extremity Interpretation of results Urgent Values: > 45 mcg/ml will be phoned to a responsible caregiver Therapeutic Range: 10 20 mcg/ml Urgent Values: > 45 mcg/ml will be phoned to a responsible caregiver Note: Pharmacy utilizes the test results reported by the laboratory to calculate true peaks and troughs that are utilized in decision making regarding dose changes. The pharmacist contacts the provider with their recommendation and places a note in the chart.

Notes:

Coen Dugan Age 8